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Enzymes- biological catalysts

Protein catalysts that can
accelerate reaction rates
as much as 1017 – typical
acceleration is 107/108
over uncatalyzed
reactions

RNA (ribozymes) can also
catalyze self-splicing
reactions – 1989 Chemistry
Nobel Prize Sydney Altman
and Tom Cech (CU-Boulder)

How much difference
can an enzyme make ?

Urea is one of the major breakdown products
of proteins and one of the main ingredients of
urine. The enzyme urease enhances the rate of
urea hydrolysis at pH 8 and 20oC by a factor
of 1014. If a given quantity of urease can
completely hydrolyze a given quantity of urea
in 5 minutes, how long, in years, would the
reaction take in the absence of the urease
enzyme?

ANSWER: Almost a billion years
(9.51 x 108 years) – that’s a long time
to have to wait to pee!
Importance of Enzymes
–
–
IMPORTANCE
OF ENZYMES
Metabolic Regulation Virtually all important
reactions in cell are controlled
by enzymes;
Thus essentially all of the
regulation of metabolism by
the cell is based on
controlling the concentration
and activity levels of enzyme
IMPORTANCE
OF ENZYMES
Theoretical – some enzymes
approach catalytic perfection, e.g.
rxn rate is determined only by
how fast substrates encounter
enzymes; model for how to make
reactions go fast.
Perfect enzymes are rare and
catalyze very important reactions
in a cell such this key step in
glycolysis – the main energy
pathway in the cell.
Chemists study for perfect
enzymes to learn how to make
the most efficient catalysts.
Drugs are often enzyme inhibitors: Penicillin
inhibits enzyme responsible for catalyzing the
formation of cell walls in bacteria
The Nature of Enzyme Catalysis
● An Enzyme provides a catalytic surface in a cleft
or groove on the surface of an enzyme called the
Active site.
.
Active site – pocket or groove on the surface on the enzyme where catalysis occurs
B
A
A
B
Active site
Juang RH (2004) BCbasics
Stereo Specificity
A
Enzymes are Highly specific –typically catalyze 1
reaction in the cell andcan distinguish between
stereoisomer substrates;
sp3
D
B
Enzyme surface
C
The tetrahedral structure
of carbon orbital has rigid
steric strain which makes
the basic building unit of
protein conformation
D
B
C
C
B
D
These two triangles are
not identical
Juang RH (2004) BCbasics
Link to Intro Enzyme animation

Link to Lew Port Enzyme animations
Figure 6.15 The catalytic cycle of an enzyme
Models of Enzyme Action
LOCK AND KEY


Enzyme structure is rigid.
Substrate is exact
complement to active site
shape of enzyme
INDUCED FIT

-
Enzyme structure changes
upon binding of substrate
Enzyme structure is flexiblecurrently accepted model.
Enzyme binds substrate
loosely, transition state tightly
Conformational changes in yeast
hexokinase on binding glucose.
Figure 6.14 The induced fit between an enzyme and its substrate
Link to enzyme animation of induced fit
• Link to induced fit 2 animation
• Link to hexokinase induced fit
Specificity – How does the enzyme
discriminate between different substrates?

Consider the example of serine proteases, a
family of enzymes that have a serine in their
active site and specifically cleave proteins at
particular amino acid sequences.
What are the features of the active sites
make one enzyme specific for each different
sequence?
Specificity of Ser-Protease Family
Trypsin
Chymotrypsin
Elastase
cut at Lys, Arg
cut at Trp, Phe, Tyr
cut at Ala, Gly
O
O
–C–N–C–C–N–
C
O
O
–C–N–C–C–N–
Shallow and
non-polar
pocket
Non-polar
pocket
Active Site
Juang RH (2004) BCbasics
Deep and negatively
charged pocket
O
O
–C–N–C–C–N–
C
C
C
C
NH3
+
COOC
Asp
Specificity – How does the enzyme
discriminate between different substrates?

In other words, how does the active site only
bind the correct substrates?

Key: Active site is complementary to
its substrate in size, shape and
distribution of charge
Link to Interactive Biochemistry
